Antagonism between the metabolic responses induced by epinephrine and piroxicam on isolated rat hepatocytes

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most employed therapeutic agents. They have a wide spectrum of biological effects, some o f which are independent of cyclooxygenase inhibition, such as the alteratio ns on the components of signal transduction systems. In particular, previou s data from our laboratory suggested an antagonism between epinephrine and piroxicam, one of the most prescribed NSAIDs. Thus, this study deals with t he epinephrine-piroxicam antagonism recorded for metabolic responses in iso lated rat hepatocytes. The obtained results show that epinephrine stimulate s lactate and ethanol consumption, stimulates glucose release from lactate only, and has no effect on cellular triacylglycerides content. Otherwise, i n a dose-dependent basis, piroxicam stimulates lactate and ethanol consumpt ion accompanied by an increase in triacylglycerides content, without change s in glucose release by hepatocytes. Piroxicam blocks the epinephrine-induc ed stimulation of glucose release from lactate, and epinephrine blocks the piroxicam-mediated increase in triacylglycerides content from lactate or et hanol. In contrast, the effects of epinephrine and piroxicam, promoting the consumption of lactate and ethanol, are not antagonized or added after the simultaneous administration of both compounds. This last result is probabl y related to the ability of both compounds to stimulate oxygen consumption. On isolated rat liver mitochondria, mu molar doses of piroxicam partially uncouple oxidative phosphorylation, and paradoxically stimulates an ATP-dep endent mitochondrial function as citrullinogenesis. These results show for first time, on isolated rat hepatocytes, an antagonism between the metaboli c responses of epinephrine and piroxicam, at the concentration found in pla sma after its therapeutical administration. (C) 1999 Elsevier Science B.V. All rights reserved.